Abstract
We previously demonstrated that TNFα induces rapid apoptosis of human peripheral blood neutrophils. To understand better the in vivo significance of neutrophil apoptosis, we examined using rats TNFα induced apoptosis of neutrophils obtained from various sources. Normal peripheral blood neutrophils (PBN) underwent significant apoptosis, but peritoneally exudated neutrophils (PEN), peripheral blood neutrophils obtained from rats i.p. injected with inflammation inducing agents (inflammatory PBN), and bone marrow neutrophils were resistant to apoptosis induced by TNFα.
Addition to TNFα of cycloheximide in a low concentration that alone were barely able to induce neutrophil apoptosis, enhanced apoptosis of PBN, inflammatory PBN and bone marrow neutrophils but not of PEN, suggesting that in the former three sources of neutrophils certain apoptosis inhibitory protein (s) were synthesized by stimulation with TNFα, and in PEN these protein (s) had been already synthesized in vivo during migration through endotherial spaces.
We further examined in vivo clearance of neutrophils by i.v. injection with 51Cr labelled neutrophils and found that PBN are promptly scavenged in the liver and the spleen.